E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Limited Stage Small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041069 |
E.1.2 | Term | Small cell lung cancer limited stage |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the phase I part of this study is to determine the recommended Phase 2 dose of pemetrexed, cisplatin, and involved-field radiotherapy in the treatment of patients with LS-SCLC.
The primary objective of the phase II part of this study is to further delineate the activity of this regimen at the recommended dose in terms of overall response rate
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: • to determine the maximum tolerated dose of pemetrexed, cisplatin and involved-field radiotherapy. •to determine the quantitative and qualitative dose-limiting toxicities of pemetrexed in combination with cisplatin and curative thoracic radiation therapy in this patient population. • further characterization of acute and late toxicities • to document objective best overall response Phase II: Secondary objectives of the study include the following: • further characterization of acute and late toxicities, • to determine complete response rate • to assess time-to-event: - Time to progressive disease - Duration of Response - Overall Survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria: [1] Histologic and/or [cytologic] diagnosis of LS-SCLC, without cytological proven malignant pleural effusion and confined to one hemithorax as defined by the IASLC 1989 criteria ( [2] Performance status of 0 to 1 on the ECOG performance status schedule [3] no prior chemo- and/ or prior thoracic radiotherapy [4] Measurable disease defined by: • At least one unidimensionally measurable lesion meeting RECIST criteria [5] adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x10e9/L, platelets ≥100 x10e9/L, and hemoglobin ≥9 g/dL. Hepatic: bilirubin < or = 1.5 times the upper limit of normal (x ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) < or = 3.0 x ULN. Renal: calculated creatinine clearance (CrCl) ≥60mL/min based on the standard Cockroft and Gault formula [6] adequate pulmonary function as defined as a Forced Expiratory Volume in 1 sec (FEV1) > 30% predicted normal value and diffusion capacity (DLCO) > 40% predicted normal value. [7] unlikely to be at excessive risk for radiation pneumonitis as defined by a V20 of ≤36% and able to drain 3rd space fluids [8] Patient compliance and geographic proximity that allow adequate follow-up. [9] Patients must sign an informed consent document. [10] Patients must be at least 18 years of age. [11] For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test and must not be lactating. For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [12] Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [13] Completion or withdrawal from this study or any other study investigating pemetrexed. [14] Patients with myocardial infarction within the preceding six months or symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia. [15] Diagnosis of a serious concomitant systemic disorder (for example, active infection including HIV) that, in the opinion of the investigator, would compromise the patient’s ability to complete the study. [16] Prior radiotherapy to the lower neck or abdominal region. [17] Discovery of a second primary malignancy that is clinically detectable at the time of consideration for study enrollment. [18] Significant weight loss (that is, U>10%) over the previous 6 weeks before study entry. [19] Concurrent administration of any other antitumour therapy. [20] Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose ≤1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). [21] Inability or unwillingness to take folic acid or vitamin B12 supplementation. [22] Inability to take corticosteroids. [23] Inability to comply with protocol or study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for Phase I is the determination of the recommended Phase II dose of pemetrexed, cisplatin, and involved-field radiotherapy for subsequent evaluation in the treatment of patients with LS-SCLC.
The primary endpoint for Phase II is to further delineate the activity of this regimen at the recommended dose in terms of overall response rate.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study (trial) is the date of the last visit or last scheduled procedure shown in the Study Schedule for the last active subject in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |